One of the fundamental problems facing cancer research is to determine how the various carcinogenic agents overcome the normal control of cell division. How such a myriad of environmental factors, chemical compounds and viruses can all act on a control system which may be common to all mammalian cells. The answers to these questions await the identification of what these cellular control mechanisms are. We have identified what may be one element of this cellular control mechanism. This is a specific isoaccepting tRNA, tRNA4lys. The objective of this research is to determine the mechanisms which control the levels of tRNA4lys in eukaryotic cells and to determine the role tRNA4lys plays in cell division. This tRNA appears to be universally present in all mammalian cells which are capable of undergoing division. Furthermore the levels of this tRNA correlate directly with the growth rate of cells in culture. RPC-5 chromatography reveals that a series of at least 5 different tRNA modification reactions are related to tRNA4lys synthesis and these enzymes appear to be controlled by different growth conditions. By isolating several of the tRNA species related to tRNA4lys and determining the modified base composition by High Pressure Liquid Chromatography and mass spectrometer we hope to describe the reaction sequence and demonstrate the appropriate tRNA modification enzymes needed for tRNA4lys synthesis. The control of the activity of these enzymes by serum, hormones, and cyclic nucleotides will be measured both in vivo and in vitro. We feel that these and other factors my control cell division by regulating tRNA4lys biosynthesis. A model is presented for the function of tRNA4lys in the early G1 phase of the cell cycle. This model will be tested using synchronized cells, cell to cell hybridizations and RNA uptake experiments. This model explains the variable length of the G1 phase, the transition from G1 to G0 and provides a basis to explain the rapid proliferation seen in cancer cells.